DISPLACEMENT OF CORTICOTROPIN-RELEASING FACTOR FROM ITS BINDING-PROTEIN AS A POSSIBLE TREATMENT FOR ALZHEIMERS-DISEASE

Article

关键词: FACTOR-LIKE IMMUNOREACTIVITY;    CENTRAL NERVOUS-SYSTEM;    FACTOR RECEPTORS;    HUMAN-PLASMA;    RAT;    CRF;    DIAGNOSIS;    DISORDERS;    DEMENTIA;    BEHAVIOR;   

DOI  :  10.1038/378284a0

来源: SCIE

【 摘 要 】

In Alzheimer's disease (AD) there are dramatic reductions in the content of corticotropin releasing factor (CRF)(1-4), reciprocal increases in CRF receptors(1,2), and morphological abnormalities in CRF neurons(5) in affected brain areas. Cognitive impairment in AD patients is associated with a lower cerebrospinal fluid concentration of CRF(6), which is known to induce increases in learning and memory in rodents(7-9). This suggests that CRF deficits contribute to cognitive impairment. The identification in post-mortem brain of CRF-binding protein (CRF-BP)(10,11), a high-affinity binding protein that inactivates CRF, and the differential distribution of CRF-BP12 and CRF receptors(13), provides the potential for improving learning and memory without stress effects of CRF receptor agonists(14). Here we show that ligands that dissociate CRF from CRF-BP increase brain levels of 'free CRF' in AD to control levels and show cognition-enhancing properties in models of learning and memory in animals without the characteristic stress effects of CRF receptor agonists.

【 授权许可】

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